Low stress flowable compositions

ABSTRACT

A photopolymerizable and photocleavable (P&amp;P) resin monomer is derived from a reactive photoresponsible moiety via various linkages to form photopolymerizable monomers and/or oligomers.

FIELD OF THE INVENTION

This invention relates to photopolymerizable & photocleavable resinmonomers and resin composite compositions, which feature by its uniquebalanced overall performance including very low polymerization shrinkageand very low shrinkage stress as well. The photoreactive moietyincorporated into such new resin's main frame enable to make the resinand/or the cured resin networks that are based upon such resinphotocleavable. Thus the polymerization rate of free radical reactionfor (meth)acrylate-based resin systems should be substantially reducedsince it alter the network formation process and consequently allow theshrinkage stress getting relief significantly. In addition, it isexpected that radically polymerizable resin systems containing such P&Presin would find wide range application in microelectronic, specialcoating and restorative dentistry where the dimensional stability andcontraction stress within cured materials are critical to the totalperformance. The invention also relates to relates to compositions thathave exceptionally low curing stress, which are comparable toconventional low stress composite, and have substantial flowability,which is comparable to conventional flowable composite. The dentalmaterials from such compositions with such unique property is for use inthe dental arts in the treatment of teeth

BACKGROUND OF THE INVENTION

Highly cross-linked polymers have been studied widely as matrices forcomposites, foamed structures, structural adhesives, insulators forelectronic packaging, etc. The densely cross-linked structures are thebasis of superior mechanical properties such as high modulus, highfracture strength, and solvent resistance. However, these materials areirreversibly damaged by high stresses due to the formation andpropagation of cracks. Polymerization stress is originated frompolymerization shrinkage in combination with the limited chain mobility.Which eventually leads to contraction stress concentration and graduallysuch a trapped stress would released and caused microscopically thedamage in certain weak zone like interfacial areas. Macroscopically itwas reflected as debonding, cracking, et al. Similarly, The origin ofcontraction stress in current adhesive restorations is also attributedto the restrained shrinkage while a resin composite is curing, which isalso highly dependent on the configuration of the restoration.Furthermore, non-homogeneous deformations during functional loading candamage the interface as well as the coherence of the material. Variousapproaches have been exploring by limiting the overall stress generationeither from the restorative materials, or by minimizing a direct stressconcentration at the restored interface. It included, for example, newresin, new resin chemistry, new filler, new curing process, new bondingagent, and even new procedure.

There have been tremendous attention paid on new resin matrixdevelopment that could offer low polymerization shrinkage and shrinkagestress. For example, various structure and geometry derivatives of(meth)acrylate-based resin systems; non-(meth)acrylates resin systems,non-radical-based resin system. In addition, for light curable, lowshrink dental composites, not only new resin systems and newphotoinitiators, new filler and filter's surface modification have alsobeen extensively explored, such as filler with various particle size andsize distribution, from nanometer to micrometer, different shape,irregular as milled or spherical as-made. It can also be different incomposition like inorganic, organic, hybrid. Although an incrementalimprovement has been achieved with each approach and/or their mutualcontribution, polymerization stress is still the biggest challenge incured network systems.

According to one aspect of the invention, a new kind of resincomposition is provided. However, unlike conventional resin system, anew concept is involved in designing such a new resin composition, whichwould render the polymerization stress in post-gel stage to asubsequent, selective network cleavage in order to have the stresspartially released. As mentioned above, all of previous arts towards lowshrink and low stress are based on the limitation on the shrink andstress formation in general. However, the shrinkage and stressdevelopment in cured network system should have two different stages: apre-gel phase and a post-gel phase. Actually, most efforts of currentarts are focussed on the pre-gel stage and some of them were proved tobe effective. Unfortunately, these approaches become ineffective interms to control the stress development in post-gel stage, where theshrinkage is not as much as in the pre-gel stage but the stress turns tomuch more sensitive to any polymerization extend. It is the immobilitynature of the increasing cross-link density within the curing systemthat leads to the increasing stress concentration within the curingsystem, period. Even worse, the problem does not stop here and thetrapped stress would eventually get relief from slow relaxation, whichcan create additional damage on a restored system. Therefore, ourapproach is based on such a concept that in the post-gel stage if someof “closed net” of any cross-linked system can be selectively broken topromote an extended stress relief period, the total stress concentrationwould be substantially reduced. To fulfil such a task, aphotopolymerizable and photocleavable resin is proposed and a generalmolecular constitution is designed. It was expected that such a resinmonomer can be polymerized like any other resin monomer but itsmainframe is able to be triggered to break upon additional light sourcesuch as near UV is blended. This is a typical photocleavable process,but it is its capability to be photopolymerized and embedded into across-linked system make it unique. In addition, it also makes possibleto avoid regenerating any leachable species through such secondarybreakage.

Photocleavage is nothing new in solid synthesis of peptides, from whichnew peptides was directed on certain template in designed sequence, thenit was cleaved from its template via a subsequent light exposure. Thereis no chemical contamination with such a process. On the other hand,photoacid and photobase could be viewed as extended applications forphotocleavage. Acidic or basic component is temporally latent to avoidany unwanted interaction with others in the system and they can bereleased on demand such as light exposure to trigger the regeneration ofthe acid or base, which then act as normal acidic or basic catalyst fornext step reactions. Recently, thermally removable or photo-chemicallyreversible materials are developed in order to make polymer or polymericnetwork depolymerizable or degradable for applications such as easilyremoving of fill-in polymer in MEMS, thermally labile adhesives,thermaspray coatings and removable encapsulation et al. Most recently,photoclevable dentrimers are explored in order to improve the efficiencyfor drug delivery. Based on our knowledge, there is no prior artinvolved photocleavale segment in cured network for contract stresscontrol. However, all of those related arts could be used as a practicalbase to justify this investigation.

Dental composite is formulated by using organic or hybrid resin matrix,inorganic or hybrid fillers, and some other ingredients such asinitiator, stabilizer, pigments et al so as to provide with thenecessary esthetic, physical and mechanical property for toothrestoration. It is well known that polymerization shrinkage from cureddental composite is one of dental clinicians' main concerns when placingdirect, posterior, resin-based composite restorations. Although thereare evolving improvements associated with resin-based compositematerials, dental adhesives, filling techniques and light curing haveimproved their predictability, the shrinkage problems remain. In fact,it is the stress associated to polymerization shrinkage that threatenmarginal integrity and lead to marginal gap formation and microleakage,which may contribute to marginal staining, post-operative sensitivity,secondary caries, and pulpal pathology.

A common approach to redue the polymerization shrinkage of dentalcomposite is to increase the filler loading, especially for posteriorrestoration. However, the higher viscosity of these highly filledcomposites may not adapt as well to cavity preparations. ¹⁻²It has beendemonstrated that to initially place a flowable composites which, withless filler content, have greater flexibility, could reduce microleakagethan direct application of microhybrid and packable compositerestorations, ³⁻⁴but this benefit may be offset by the increasingpolymerization shrinkage for the flowable composite itself.⁵ Therefore,it is also highly desirable to develop low shrinkage, especially lowcuring stress flowable composite, in order to really reduce microleakageas mentioned above.

The challenge in developing any dental composite is to balance theoverall performance, including esthetic appearance, handling characteras well, in addition to low curing stress and necessary mechanicalstrength. Unfortunately, superior mechanical strength usually is aresult of increasing cross-linking density, from which an unwantedpolymerization shrinkage and shrinkage stress always accompanied. Thereis increasing effort to develop new resin systems in the attempt tominimize such a shrinkage and stress accordingly. For example, reducingthe polymerizable proups in the resin matrix by designing resin monomerwith different size and shape indeed work well to some extent in thisregard. However, it is usually resulted in decreasing mechanicalstrength and losing certain handling characteristic because of thelimited molecular chain mobility and the limited polymerizationconversion. In addition the shrinkage can also be reduced by usingspecial filters which allow an increase in filler loading withoutcompromising too much in handling property. Even so, the curing stressfrom most of flowable composites remains substantially high. Obviously,it is highly desirable to develop flowable dental composition with lowcuring stress.

DESCRIPTION OF THE PREFERRED EMBODIMENTS

Theoretically speaking, if any kind of environmentally sensitive moiety,such as a thermally cleavable or photo-labile linkage were incorporatedinto polymerizable resin monomers, such resin or its resulting polymericmaterial would become command-responsible, more specifically enable themthermo-cleavable or photo-cleavable. The chemistry of some classicalphoto-initiators could be adopted as the base for designing suchphotopolymerizable and photocleavable resin monomers, because such aninitiator was explored as polymerizable photoinitiator ormacroinitiator. However, none of them were really incorporated intopolymer chain or polymeric network to make the polymeric chain ornetwork breakable one way or another.

It is the another objective of this investigation to develop a new resinsystem for next generation low shrink and low stress restorativematerials by incorporating a photocleavable or thermally liable moietyas part of a photopolymerizable resin monomer. It was expected with suchan unusual approach it would enable a conventional polymerized networkshould be selectively cleavaged, thus to disperse the stress frompostpolymerization and furthermore to result in a self stress-relief,ultimately to minimize the overall stress concentration.

In order to make a polymerized network cleavable-on-command by light orphotocleavable, a light responsible moiety should be stable towardsstandard light exposure process such as visible light curing untiladditional exposure to specific light with distinguished energy level.In particular, such energy source can be anything other than thestandard visible blue light. Near UV light would be one of typicalexamples among the many possible choices. Furthermore, it was expectedthat compounds derivated from ortho-nitrobenzyl segment or fromα-hydroxyalkylphenone should be ideal candidates for this new classresin monomers that be photopolymerized by visible light and betriggered to be breakable by extra UV light if needed.

Its feasibility of this approach allows a rapid exploration on itsversatility for a new class of resin. Accordingly, a variety of suchpolymerizable and photocleavable resin monomers were successfullyprepared with wide range of viscosity as illustrated in Scheme II.

Furthermore, such new resin monomer was formulated with otherconventional resin monomers like BisGMA, TEGDMA, UDMA or experimentalresin monomer like macrocyclic resin in a variety ratio in order to haveoverall performance got balanced for the resulting composites. As showedin the following examples, remarkable low shrinkage, low stress andexcellent mechanical property plus the good handling characteristicswere demonstrated by those composites based on such new class P&P resinmonomers.

TABLE I Polymerization Shrinkage and Stress for Various Activated ResinMix Shrinkage (%) Stress by Helium (MPa) by Pycnometer TensometerDenfortex Resin 10.2 4.1 TPH Resin/999446 6.8 4.5 TPH Resin/999447 7.34.3 Harpoon Resin/xj5-12 5.5 3.1 Harpoon Resin/xj5-26 5.8 3.2 LB5-158-15.2 1.4 LB5-158-2 5.7 2.0 LB5-167-2 6.5 1.9 LB5-167-3 6.2 1.5 LB5-167-46.9 1.5

TABLE II Polymerization Shrinkage, Stress and Microstrain for VaariousComposites Shrinkage (%) Microstrain Stress by Helium (ue) by (MPa) byPycnometer Strain Gage Tensometer TPH/A2 3.10 1600 2.9 EsthetX/A2 2.921995 2.5 SureFil/A 2.09 1840 2.7 Supreme/A2B 2.65 1720 N/A Supreme/YT2.39 2005 N/A Harpoon/A2 1.34 1000 1.7 Harpoon/A3.5 1.70 N/A 1.8Harpoon/B1 1.31 N/A 1.5 Harpoon/B2 1.61 N/A 1.9 Harpoon/CE 1.70 N/A 1.9LB5-156 0.87 N/A 1.5 LB5-153 0.93 N/A 1.4 LB5-160 0.36 N/A 1.4

According to the present invention there is provided a composition ofmatter that can be polymerized via an energy source, containing portionswithin the new composition of matter that are reactive to a secondenergy source. The invention also provides a composition of matter thatcan be polymerized via an energy source, containing portions within thenew composition of matter that are reactive to a second energy sourceand that upon activation of the second source of energy, de-polymerizeand/or degrade. A composition of matter is also provided that can bepolymerized via a first energy source, containing portions within thenew composition of matter that are reactive to a second energy sourceand that upon activation of the second source of energy, de-polymerizeand/or degrade without substantially effecting the structural propertiesof the material polymerized by the first energy source. A furthercomposition of matter is provided that can be polymerized via a firstenergy source, containing portions within the new composition of matterthat are reactive to a second energy source and that upon activation ofthe second source of energy, de-polymerize and/or degrade to elevatestress created during the polymerization of the composition of mattercreated via the first energy source without substantially effecting thestructural properties of the material polymerized by the first energysource. According to another aspect of the invention, a composition ofmatter is provided that comprises monomers, prepolymers and/or polymersthat can be polymerized via an energy source (thermal, photochemical,chemical, ultrasonic, microwave, etc.), containing portions within thenew composition of matter that are reactive to a second energy source(thermal, photochemical, chemical, ultrasonic, microwave, etc.).

Thus, certain limitations of the heretofore known art have beenovercome. Polymer networks with cross-linking are desired for strengthproperties, but lead to higher degree of shrinkage and stress. Thisinvention allows formation of cross-linking, while at the same time,providing a mechanism (the second form of energy application) thatrelieves the stress created while maintaining the structural integrityof the polymer network created. Relief of stress during polymerizationhas been desired and typically approached through attempt to relieve thestress during the “pre-gel” state of polymerization, prior to the“post-gel” state, wherein the polymer network has now been established,cross-linked set up and, due to the more rigid state, stress is created.The invention substantially eliminates the stress during this “post-gel”state. There are prior known systems for materials that arereversible—that is, once polymerized, some form of post-polymerizationenergy is applied to fully decompose or degrade the polymer network to astate that renders the material unusable. In the present invention,there is provided only partially, in a controllable manner, degrading ordecomposing a portion of the polymer network and maintaining theintegrity of the polymer network.

As discussed above, according to one embodiment of the presentinvention, a photopolymerizable and photocleavable resin monomer(hereinafter referred to as the “P&P” resin) offers unique combinationof low curing stress and good mechanical strength. The inventive P&Presin features by incorporating a photoresponsive moiety within theresin monomer and is a (meth)acrylate based resin and capable of beingpolymerized as any other conventional (meth)acrylate monomers. However,the presence of such a photoresponsive moiety enables P&P resin topolymerize in a way different from those conventional (meth)acrylatemonomers. More specifically P&P resin polymerize with a unique curingkinetic, which allow stress relief through the relatively slow curingprocess without compromising the overall mechanical strength.Consequently substantially low polymerization shrinkage stress resultsfrom P&P resin and P&P resin based composite, as compared to thoseconventional resin like BisGMA/TEGDMA or EBPADMA, and other conventionalcomposites. Typical posterior composites based on the inventive P&Presin and loaded 80-82% (wt/wt) of inorganic fillers offer shrinkagestress of 1.3-1.7 Mpa. They can also demonstrate good mechanicalstrength. The present invention is extended application of P&P resin. Itwas unexpectedly discovered that an exceptionally low curing stressremained even with lowering filler loading, which paved a way to lowstress flowable composite. The filler level varies from 1% to 70%,wt/wt, preferably, 10-60%, wt/wt, and more preferable 50-60%, wt/wt. Theconventional resin monomers can also be incorporated by up to 40-50%,wt/wt with P&P resin, depending upon the nature of such conventionalresin monomer and the end use. The filler composition can be adjusted aswell.

As showed in Table I through II, an exceptionally low shrinkage stresswas revealed from these new flowable compositions. Similar flowablepastes were also formulated by using TPH resin (999446 and availablefrom DENTSPLY International) with the same filler loading andcomposition as a control. As expected a much higher shrinkage stressresulted, 3.6 MPa vs. 0.9-1.3 MPa. FIG. 1 shoes a comparison between thetypical experimental flowable composites (LB6-109, 110, 111 and XJ5-196)and some of commercially available flowable materials, such asDyractflow (DENTSPLY International), AdmiraFlow (VOCO, Germany), Flow It(Jeneric/Pentron, Inc.), EsthetXflow (DENTSPLY International),Revolution (KERR CORPORATION), and Tetric Flow (IVOCLAR VIVADENT, INC.).There is up to 60-80% (percent) stress reduction achieved by theexperimental flowable composite as compared with EstheXflow andDyractflow. In addition, the new flowable material still offers moderatemechanical strength, which is comparable to most flowable products (seealso in FIG. 2). It is expected that the mechanical strength can befurther improved by refining the filler compositions.

The low stress nature demonstrated by P&P resin and its composites isattributed to the unique curing kinetic as discussed above. PDC studyfurther confirmed this unique, moderately slow polymerization rate ascompared to TPH resin or its composite. TetricFlow also demonstrated aslow polymerization rate (under same curing condition) due to thepresence of a stable radical compound. TetricFlow has a relatively lowerstress than other commercially available flowable materials (3.3-4.6MPa), but it still generates a much higher shrinkage stress (2.4-3.2MPa) than the experimental flowable composites based on P&P resin(1.0-1.4 MPa).

The present invention provides flowable composites with an exceptionallylow polymerization stress of 0.9-1.3 MPa, which is about 60-70% lessthan that of typical EsthetXflow (3.4 MPa) or Dyractflow (4.6 MPa). Moreimportantly, the new flowable material can still offer moderatemechanical property. This unique property combination regarding lowcuring stress and handling character enable to be used as dentalrestoratives like liners, sealants, et al and other application fieldwhere curing stress and flowability is critically concerned.

TABLE I General Physical Property for Activated Neat P&P Resin Systems100% TPH Resin 100% P&P Resin 100% P&P Resin 100% TPH Resin (999452)(LB6-71) (w/TEGDMA) (EBR6983) (w/TEGDMA) (999446) 0.15% CQ 0.15% CQ0.15% CQ 0.165% CQ 0.20% EDAB 0.20% EDAB 0.20% EDAB 0.30% EDAB 0.02% BHT0.02% BHT 0.02% BHT 0.025% BHT Lot # LB5-187-1 LB6-106-1 LB6-114 030804Viscosity at 20° C., poise 150 500 1020 150 Uncured density, g/cm³1.1206 1.1129 1.1162 1.1210 Cured density, g/cm³ 1.2077 1.1888 1.18671.2099 Shrinkage @ 24 hrs., % 7.2 6.4 5.9 7.4 Stress @ 60 min., MPa 4.51.8 1.4 4.7 ΔH₁ in N2 @ mode 1 110 t_(o), seconds 15 t_(max), seconds 31ΔH₁ in N2 @ mode 2 138 120 107 133 t_(o), seconds 13 17 17 10 t_(max),seconds 31 35 36 29

TABLE II Properties of New P&P Resin-Based Flowable Composites PastesLB6-110 XJ5-196 LB6-116 XJ5-190 Resin Composition LB6-106-1 LB6-106-1LB6-114 TPH Resin (40%) (40%) (40%) (40%) Filler Composition LB6-91-3LB6-91-3 LB6-91-3 LB6-91-3 (60%) (60%) (60%) (60%) Viscosity at 20° C.,poise 8000    4300    9300    2000    PZN Enthalpy ΔH (Vis/UV) (Vis/UV)(Vis/UV) (Vis/UV) (J/g) by PDC in N2 46/ 48/ 45/51 54/ Induction TimeΔt_(ini) 17/ 14/ 14/13 11/ (seconds) by PDC N2 Peak Time Δt_(max) 34/32/ 31/29 22/ (seconds) by PDC in N2 Uncured density (g/cm3)   1.7201  1.7179   1.7228   1.7294 Cured density (g/cm3)   1.7875   1.7829  1.7860   1.8049 Shrinkage (%) by pycnometer 3.8 3.6 3.5 4.2 @ 20 hrslater Shrinkage Stress 1.1 0.9 0.9 3.6 (MPa) by tensometer FlexuralStrength (MPa) 101 +/− 5  109 +/− 6  109 +/− 5  111 +/− 9  Modulus (MPa)4000 +/− 130 4700 +/− 190 4600 +/− 110 5250 +/− 200 Compressive Strength(MPa) 286 +/− 8  277 +/− 13 283 +/− 3  383 +/− 11 Modulus (MPa) 5000 +/−150 4900 +/− 450 5260 +/− 330 4500 +/− 250

Thus, it should be evident that the invention as disclosed hereincarries out one or more of the objects of the present invention setforth above and otherwise constitutes an advantageous contribution tothe art. As will be apparent to persons skilled in the art,modifications can be made to the preferred embodiments disclosed hereinwithout departing from the spirit of the invention, the scope of theinvention herein being limited solely by the scope of the attachedclaims.

1. A method of reducing stress during curing of a polymerizable materialof the type having a cross-linked network with a pre-gel phase and apost-gel phase, the improvement comprising selectively breaking at leasta portion of the cross-link network thereby inducing a stress-reliefperiod.
 2. A method as in claim 1, wherein the polymerizable is aphotopolymerizable and photocleavable resin.
 3. A method as in claim 2wherein said resin is photocleavable upon exposure to UV light.
 4. Amethod as in claim 2 wherein said resin has a segment selected from thegroup consisting of ortho-nitrobenzyl and α-hydroxyalkylphenone.
 5. Adental material comprising a photopolymerizable and photocleavableresin, wherein said resin forms a cross-linked network upon curing andwhich as a pre-gel and post-gel phase; at least a portion of saidcross-linked network being breakable upon exposure to light.
 6. A dentalmaterial as in claim 5, wherein said resin has a segment selected fromthe group consisting of ortho-nitrobenzyl and α-hydroxyalkylphenone. 7.A dental material as in claim 5, wherein said light is in the UV range.